# RX871024

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**RX871024** is an [experimental drug](/source/Experimental_drug) containing an [imidazoline](/source/Imidazoline) moiety, developed by [Reckitt Benckiser](/source/Reckitt_Benckiser).[1] The development of RX871024 was discontinued in 1997. It is known for its potent ability to enhance [insulin](/source/Insulin) action. RX871024 stimulates insulin secretion from [pancreatic beta cells](/source/Pancreatic_beta_cell) through multiple mechanisms.[2]

## Mechanism of action

Unlike traditional [sulfonylureas](/source/Sulfonylurea), RX871024 not only closes [ATP-sensitive potassium](/source/ATP-sensitive_potassium_channel) (KATP) channels—leading to membrane [depolarization](/source/Depolarization), opening of [voltage-gated calcium channels](/source/Voltage-gated_calcium_channel), and increased intracellular [calcium](/source/Calcium_in_biology)—but also directly stimulates [exocytosis](/source/Exocytosis) of insulin-containing granules, even under conditions where calcium levels are held constant.[3][4]

This compound inhibits several potassium channels, including KATP, [KCa](/source/Calcium-activated_potassium_channel), and [delayed rectifier potassium channels](/source/KvLQT1), and interacts specifically with the [Kir6.2](/source/Kir6.2) (KCNJ11) subunit of the KATP channel, distinguishing its mode of action from sulfonylureas, which target the [sulfonylurea receptor 1](/source/ABCC8) (ABCC8).[4][5] Additionally, RX871024 mobilizes calcium from intracellular, [thapsigargin](/source/Thapsigargin)-sensitive stores via [redox](/source/Redox)-dependent pathways involving [cytochrome P-450](/source/Cytochrome_P-450).[3] Its insulinotropic effect is further enhanced by activation of [protein kinase C](/source/Protein_kinase_C) and increases in [diacylglycerol](/source/Diacylglycerol) (DAG) levels, while [protein kinase A](/source/Protein_kinase_A) activity appears to play a permissive role.[5][6] RX871024 also modulates the [phosphorylation](/source/Phosphorylation) of cytosolic proteins such as nonmuscle [myosin heavy chain-A](/source/MYH9), which may be involved in insulin secretion signaling.[6]

Collectively, these multifaceted actions make RX871024 a potential lead compound for the development of novel antidiabetic therapies.

## Synthesis

Ex 1: The reaction between ethyl 1-phenyl-1H-indole-2-carboxylate [20538-24-3] (1) and ethylenediamine (2) gives RX871024 (3).

Prec:[7] Patent:[8] Also, reaction of 1-phenylindole-2-carbonitrile, [PC20095505](https://pubchem.ncbi.nlm.nih.gov/compound/20095505) with ethylenediamine monotosylate [14034-59-4] gives higher yield.

## References

1. ["RX 871024"](https://adisinsight.springer.com/drugs/800003412). *AdisInsight*. Springer Nature Switzerland AG.

1. Efendic S, Efanov AM, Berggren PO, Zaitsev SV (December 2002). "Two generations of insulinotropic imidazoline compounds". *Diabetes*. **51** (Suppl 3): S448–S454. [doi:10.2337/diabetes.51.2007.s448](https://doi.org/10.2337/diabetes.51.2007.s448). [PMID 12475789](https://pubmed.ncbi.nlm.nih.gov/12475789)

1. Efanova IB, Zaitsev SV, Brown G, Berggren PO, Efendić S (February 1998). "RX871024 induces Ca2+ mobilization from thapsigargin-sensitive stores in mouse pancreatic beta-cells". *Diabetes*. **47** (2): 211–218. [doi:10.2337/diab.47.2.211](https://doi.org/10.2337/diab.47.2.211). [PMID 9519715](https://pubmed.ncbi.nlm.nih.gov/9519715)

1. Zaitsev SV, Efanov AM, Efanova IB, Larsson O, Ostenson CG, Gold G, Berggren PO, Efendić S (November 1996). "Imidazoline compounds stimulate insulin release by inhibition of K(ATP) channels and interaction with the exocytotic machinery". *Diabetes*. **45** (11): 1610–1618. [doi:10.2337/diab.45.11.1610](https://doi.org/10.2337/diab.45.11.1610). [PMID 8866568](https://pubmed.ncbi.nlm.nih.gov/8866568)

1. Mourtada M, Smith SA, Morgan NG (June 1998). "Effector systems involved in the insulin secretory responses to efaroxan and RX871024 in rat islets of Langerhans". *European Journal of Pharmacology*. **350** (2–3): 251–258. [doi:10.1016/S0014-2999(98)00245-3](https://doi.org/10.1016/S0014-2999(98)00245-3). [PMID 9696415](https://pubmed.ncbi.nlm.nih.gov/9696415)

1. Mourtada M, Chan SL, Smith SA, Morgan NG (July 1999). "Multiple effector pathways regulate the insulin secretory response to the imidazoline RX871024 in isolated rat pancreatic islets". *British Journal of Pharmacology*. **127** (5): 1279–1287. [doi:10.1038/sj.bjp.0702656](https://doi.org/10.1038/sj.bjp.0702656). [PMC 1566128](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566128). [PMID 10455276](https://pubmed.ncbi.nlm.nih.gov/10455276)

1. Dolby LJ, Lord PD (October 1969). "2-Alkylidene-2H-indole intermediates. Thermolysis of 2-hydroxydiphenylmethylindole.". *The Journal of Organic Chemistry*. **34** (10): 2988–2993. [doi:10.1021/jo01262a042](https://doi.org/10.1021/jo01262a042)

1. ["Imidazolinyl indole derivatives useful in the treatment of diabetes"](https://patents.google.com/patent/US5385919A/en?oq=US5385919). No. 5385919.

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Adapted from the Wikipedia article [RX871024](https://en.wikipedia.org/wiki/RX871024) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/RX871024?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.